Majority of the end-stage renal disease (ESRD) patients on hemodialysis (HD) experience a substantial symptom burden, which significantly impairs their health-related quality of life (HRQOL). Additionally, patient symptoms of depression, pain and fatigue are associated with increased hospitalization and mortality, potentially mediated by behavioral factors such as non-adherence to medication and dialysis, as well as biological factors such as inflammatory cytokines. Given the limited effectiveness of prior interventions to alleviate symptoms and improve HRQOL in HD patients, and lack of evidence on their effect on bio-behavioral mediators, our proposed study fulfills a critical need for providing patient-centered dialysis care, while advancing mechanistic insights into the underlying inflammatory process. Our team has successfully demonstrated the effectiveness of a stepped collaborative care intervention (SCCI) in other chronically ill patient populations. Collaborative care provides an integrated multi-disciplinary structured management plan; and a stepped approach for pharmaco- and/or behavioral-therapy allows for individualization of treatment according to patients? clinical status, preferences and treatment response. In order to simplify the delivery of the behavioral therapy component of SCCI and reduce the associated patient and provider burdens, our multi- disciplinary team of experts in nephrology, psychology, and health technology pioneered and tested the delivery of behavioral therapy using video-conferencing in dialysis units. Our pilot study showed that this approach is feasible, acceptable and requires minimal additional resources. The goal of the proposed Technology Assisted Stepped Collaborative Care Intervention (TASCCI) study is to test the effectiveness of SCCI for alleviating symptom clusters and improving HRQOL in a multi-center randomized controlled trial of 150 diverse HD patients from Pennsylvania and New Mexico. We will compare the effectiveness of our intervention with an attention control arm of technology-delivered health education to improve key patient- centered outcomes. Specifically, we will examine 1) changes in depression (primary outcome), pain, fatigue and HRQOL after 12 week intervention (Aim 1), 2) effect on medication and dialysis adherence (Aim 2); and 3) changes in levels of inflammatory biomarkers (Aim 3). This study directly responds to call from Kidney Disease Improving Global Outcomes (KDIGO) for integration of symptom assessment and management in routine ESRD care. TASCCI may provide a feasible and resourceful approach to alleviate common patient symptoms and improve HRQOL for HD patients that could be readily adopted and integrated in routine dialysis care for wide-scale dissemination.